1. GLUTEN SENSIVITY AND ITS ROLE
IN CHRONIC FATIGUE AND
AUTOIMMUNE DISEASE
WHAT YOU NEED TO KNOW
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Copyright © 2015 The Dr.com. All rights reserved. No parts of this book may be reproduced
in any matter without prior written permission from the publisher.
By: Dr. Tom O’Bryan
DC, CCN, DACBN
Toward Healing the Planet,
One Person At A Time

2. INTRODUCTION
Even a short scan of the published medical literature on the impact of diet, specifically food
allergies and sensitivities on chronic fatigue syndrome (CFS), also known as Myalgic
Encephalomyelitis (ME) would lead you to conclude dietary modifications have no impact on
either the onset of or a recovery from the illness.
Back in 1996 researchers in the Journal of the American
Dietetic Association found no specific nutrient deficiencies in
ME/CFS and concluded diet did not play a role. Dietary
guidelines for ME/CFS remain as those recommended by the
CDC in the US and abroad; CFS patients should simply follow
the offi ial go er e t ala ed diet guideli es hi h
promotes high levels of starchy carbohydrates like gluten-
containing breads and cereals.
Could they be missing something? I propose that two
disorders associated with sensitivity to the gluten products in
grains, Celiac Disease (CD) and Non-Celiac Gluten Sensitivity
(NCGS) are vastly underdiagnosed both in the general and CFS population. In fact, studies
suggest undiagnosed gluten sensitivity contributes to early mortality.
Celiac Disease– refers to people with total villous atrophy in the gut as a result of immune
sensitivity to gluten (gliadin) which has resulted in autoimmune antibodies to the gut lining
Non-Celiac Gluten Sensitivity – includes broadly two classes of people, first those with only
partial villous atrophy or inflammation in the gut (which the current test for CD misses) induced
by sensitivity to gluten, and second, people with no gut imbalances at all but autoimmunity to
other organs and systems (e.g. thyroid) induced by sensitivity to gluten
CD is a u h greater pro le tha has pre iousl ee appre iated Archives of Internal
Medicine February 2003
Autoimmunity and Celiac Disease
Glute se siti it is a s ste i autoimmune disease with diverse manifestations…Lancet
Neurology March 2010
Autoimmune disorders are now cumulatively the third leading cause of death in the
industrialized world. Recognized in about 24 million people, autoimmune disorders are now
the leading cause of death in the U.S. (and those are only the ones that have been diagnosed).
While many individual autoimmune diseases are rare, collectively they are thought to affect
approximately 8 percent of the United States population – 24 million persons.

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To provide a context to evaluate the impact of autoimmune diseases, cancer affected
approximately 9 million people and heart disease affected approximately 22 million people in
the United States
NIH. Autoimmune Diseases Coordinating Comm.Autoimmune Diseases Research Plan 2006
With diagnostic rates at about 1 out of 3 people, some form of autoimmunity is probably
present in at least 72 million people in the US.
You are 10 times more likely to develop an autoimmune disorder if you have CD.
Yes you read that right. As you will read below, both untreated Celiac and NCGS appear to
significantly increase mortality rates and CD is being implicated in almost all autoimmune
disorders.
More than 19,000 papers on CD and the new entity NCGS have been published in PubMed.
Despite (or maybe because of) the voluminous data, no one has worked on connecting the dots
and synthesizing the results in a way that both patients and busy practitioners can get, this is
where my role comes in as a formerly busy physician myself and a functional medicine
specialist.
Dr To O Brya
I specialized in the treatment of Celiac and NCGS before giving it up to
train other Doctors and practitioners around the world full-time on the
subject. You might say, I am on a mission.
In this ebook, I aim to summarize key information from my trainings I
gave in the UK in 2011 to nutritional therapists and doctors.
I can almost guarantee your doctor or gastroenterologist or specialist
ME/CF“ do tor does t k o u h of this i for atio a d pro a l
does t grasp its potential significance in ME/CFS.
Surprised Diet Could Play a Significant Role in Such a Serious Disease as Chronic Fatigue
Syndrome?
Patients and practitioners alike may be surprised that diet can play a critical role in serious
chronic complex illnesses su h as ME/CF“. “o e a e e feel do ast that just diet a d
not a virulent bug could be the cause or a major contributor to their ME/CFS.

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Misconception and Misdiagnosis
Misper eptio s regardi g the ature of food allerg that still per eate u h of the edi al
orld are at the root of this. Classi al approa hes to u dersta di g food allergies assu e
reactions to food can only be IgE mediated. IgE produces classic allergic reactions such as
sneezing, sniffling, rashes and difficulty breathing. We know from the research, that IgE food
allergies are likely to play only a small role in ME/CFS patients.
Celiac disease (CD) and non-celiac gluten sensitivity (NCGS), however, are IgG and IgA mediated
immune responses that can cause chronic gut inflammation, and very likely chronic
inflammatory and autoimmune processes elsewhere in the body.
The I fla atory Disease Epide i
Inflammatory disorders have been increasing rapidly over the past thirty years. Chronic
inflammation and autoimmune processes are implicated in ALL of the major chronic complex
ill esses that light hu a s toda . The studies o ered i this eBook suggest a fire i the gut ;
i.e., untreated gut inflammation may increase the risk of early mortality in all major chronic
illnesses
For a variety reasons covered later, including the intriguing evidence that at least a subgroup of
the ME/CFS population has an autoimmune disorder , the facts about CD and NCGS need to be
fully understood.

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10 FACTS YOUR DOCTOR OR GASTEROENTEROLOGIST PROBABLY DOESN T KNOW ABOUT
CELIAC DISEASE AND NON GLUTEN CELIAD SENSITIVITY (NCGS)
…for every symptomatic patient with celiac disease there are eight patients with celiac disease
a d o gastroi testi al s pto s. Gastroenterology February 2001
FACT 1: Due to a historical misconception that Celiac Disease (CD) MUST present with
gastrointestinal (GI) symptoms, CD is not tested for in many patients, and thus is vastly
underdiagnosed.
The ha es are if ou ha e fe or o GI s pto s, our Do tor o t
have tested you for CD. Nor is CD part of the differential diagnosis for
ME/CFS. Unfortunately, doctors do t realise that eurologi al s pto s
and a wide range of other non-GI symptoms, most of which are found in
ME/CFS, should trigger the test for CD.
The current guidelines for celiac disease suggest testing for it where there
is chronic fatigue, short stature, delayed puberty, dental enamel defects,
elevated liver transaminase levels, dermatitis herpetiformis, and nutritional
anemias...
The brain seems to e parti ularl ul era le… PediatricsAugust 2001
CD was originally believed found in people with diarrhea, cramping, bloating, constipation and
other gastrointestinal issues, stool problems, anemia and weight loss. Further research
revealed CD and its offshoots commonly cause fatigue, weakness, osteoporosis, joint and
bone pain, migraines, numbness and tingling, depression, etc.
The i e erg is a o o odel used to e plai the epide iolog of oelia disease. The
majority of patients have what is termed silent coeliac disease, which may remain undiagnosed
e ause the o ditio has o GI s pto s. British Medical Journal July 1999

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Although celiac disease has been known for over thirty years to cause both gastrointestinal and
neurological symptoms, it took until 2000 before celiac disease was shown, in some individuals,
to cause only neurological symptoms. As late as 2010, a review article in Lancet, no less, noted
that o l re e tl has it ee a epted that elia disease a prese t ith o l eurologi al
sympto s. I fa t, it appears that ost people ith CD ho ha e eurologi al s pto s do t
have gastrointestinal symptoms.
FACT 2: A Diagnosis of celiac disease refers to the END STAGE of the disease and diagnosis of
celiac disease requires TOTAL VILLOUS ATROPHY. CD takes YEARS to manifest and is preceded
by GUT INFLAMMATION. These earlier stages may be described as part of Non-Celiac Gluten
Sensitivity (NCGS) but, like, celiac disease, also still mostly go undiagnosed and untreated
If you had a negative test for CD that ea s ou did t ha e total
villous atrophy. You could, however, have partial villous atrophy or
increased lymphocyte activity in the gut lining which standard
testing for CD misses.
The villi, with their finger-like projections, appear like shag carpets
in the gut. The villi, with their high surface area, maximise nutrient
absorption from the gut.
If you have partial villous atrophy, or no villous atrophy at all; your

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CD test will be NEGATIVE.
A large amount of inflammation in the gut can still occur in people not testing positive for CD. In
fa t, it s lear that the pro esses that result i total atroph of the illi egi u h, u h earlier
and are often evident if they are looked for. In fact, some researchers believe the search for the
roots of celiac disease should begin early in life, perhaps even in utero .
Normal Vs Atrophied Villi
Normal looking villi are on the left; total villus atrophy (required for coeliac disease diagnosis)
Total illous atroph does t o ur o er ight. The gut i fla atio u osal i traepithelial
lymphocytosis) that usually precedes the war zone-like structures occurring in total villus
atrophy, can be identified. The lymphocytes shown in brown, below, are producing the
cytokines that will eventually destroy the intestinal illi, leadi g to total illous atroph or
CD.

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Indeed, studies suggest that the degree of lymphocyte invasion present is a more effective and
certainly earlier test for gluten sensitivity than charting the degree of atrophy of the villi.
Inflammation (lymphocyte invasion) comes first, followed by damage to the villi, followed by
destruction (atrophy) of the villi.
The presence of gluten induced autoantibodies is another early test which, if the person keeps
consuming gluten, appears to be able to predict the ultimate demise of their villi – (and their
ultimate diagnosis with celiac disease.)
If we include now not only all CD, but also all those with NCGS, how many people suffer from
some form of gluten sensitivity?
312 family members (FMs) of CD disease patients were tested for all types of gluten sensitivity
i.e.: CD, subclinical and silent forms. 1 out of 5 FM tested positive – suggesting 20% of the
population have some form of gluten sensitivity
We fou d a high-prevalence of CD between CD FMs, and most of them were olygo- or
asymptomatic.
European review for medical and pharmacological sciences June 2010.

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FACT 3: Untreated Celiac Disease (CD) and Non Celiac Gluten
Sensitivity (NCGS) Is Associated with Increased Mortality Rates
Your mortality rate is HIGHER with NCGS AND CD and does not
require the end-stage of total villous atrophy
The elevated mortality risk for all causes of death combined,
reflected, for the most part, disorders characterized by immune
dysfunction Archives of Internal Medicine July 2003
A large Swedish Inpatient Registry study investigating mortality risks in more than 10,000 CD
patients over 30 years found having CD increased the risk of death from a plethora of major
diseases. The study examined standardized mortality ratio (SMR) which charts the increased
likelihood of death if you have both CD and another disease. The SMR of 11.4, for instance, in
non-Hodgkins Lymphoma (NHL), for instance, indicates a person with CD and NHL is 11.4 times
more likely to die earlier from Non-Hodgkins lymphoma than someone with that disease and no
CD.
Note that most of these disorders are associated with immune dysfunction.
 No -Hodgkins Lymphoma (SMR 11.4)
 Cancer of SI (SMR 17.3)
 Inflammatory Bowel Diseases (SMR 70.9)
 Autoimmune Diseases (including RA) (SMR 7.3)
 Diffuse disease of Connective Tissue (SMR 17.0)
 Allergic Disorders (ie.asthma) (SMR 2.8) Diabetes (SMR3.0)
 Disorders of Immune Deficiency (SMR(20.9) Tuberulosis (SMR 5.9)
 Pneumonia (SMR 2.9)
 Nephritis “MR .
The largest ever study of mortality rates found celiac disease in almost 10% of 350,000 plus
iopsies olle ted o er 0 ears, late t CD or al u osa ut positi e lood ork i a out
1% (3.7K), and inflammation but still partially intact villi in about 5% (13K) of the biopsies
Results showed increased mortality rates in all three cohort groups; startlingly, mortality rates
were highest in the inflammation (Non-Celiac Gluten Sensitive) group.
•HRs in Coeliac disease (HR, 1.39; 95%) (i.e. 39% more likely to die earlier)
•HRs in latent Coeliac disease (HR, 1.35; 95%) (35% more likely to die earlier)
•HRs in patients with inflammation (HR, 1.72; 95%) (72% more likely to die earlier)

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When Ignorance is Not Bliss
Individuals with Coeliac disease are treated with a gluten-free diet, while very few with
inflammation are. Those with inflammation may have an overall worse prognosis than those
with villous atrophy, since institution of a gluten-free diet often leads to
normalisation of the mucosa. Journal of the American Medical Association Sept 2009
What could account for such a large increase in mortality in what appeared to be the least
severely affected group? Proper diagnosis. The study authors suggested that people with celiac
disease te d to get diag osed a d heal their gut. People ith NCG“, ho e er, ofte do t get
diag osed. I their ase it s ot the elia disease that gets the ut the lo g-term
inflammatory state that increases their risk of dying from another disorder.
Focus on Children
Childre diag osed ith Coelia disease had a threefold i reased risk of lo g-term mortality.
This is in marked contrast to the experience of adult Coeliac disease where the long-term
increase of mortality was modest. The increased mortality in children from external causes may
refle t eha ioral ha ge asso iated ith opi g ith a hro i disease a d its treat e t.
American Journal of Gastroenterology April 2007
FACT 4: Having CD/NCGS and not adhering to a gluten free diet increases your risk of death 6
fold. The equivalent of 1/90th
of a slice of bread can cause severe symptoms in the most
sensitive. CD/NCGS is PERMANENT
Death was most significantly affected by diagnostic delay,
patter of prese tatio , a d adhere e to the GFD…No -
adherence to the GFD, defined as eating gluten once-per-month
increased the relative risk of death 6-fold…Our results
emphasize the need for prompt diagnosis and treatment also in
those patients with a minor or symptomless form of coeliac
disease
Lancet 2001
A Lancet study following up 1072 adult celiacs and 3384 first-degree relatives after 20 years
found the SMR of 2.0 (200%) i.e. if you have CD you are twice as likely to die early than
someone without it. Remarkably, eating even small amounts of gluten, placed celiacs at
increased risk of death.
Gluten Sensitivity is Permanent
Coelia Disease is a per a e t i tolera e to glute that results i i u ologi all

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mediated inflammatory damage to the s all i testi e u osa American Journal of Clinical
Nutrition March 1999
Gluten-related disorders are permanent; while your gut may heal, your gluten sensitivity
remains and adding gluten back into your diet will cause the inflammation to rear up again.
Studies have found that even after five years on a gluten free diet, the gut will eventually flare
up if you return to eating gluten products.
In some cases even very small amounts of gluten can cause system-wide problems.
A illigra of glute a day keeps the u osal re o ery
a ay: a ase report
Nutrition Review in Sept 2004
A frustrated 34 woman went to a Celiac specialist to find
out why, after following a gluten-free diet for a year she
was still not better. Testing revealed her antibodies were
still sky high and she had total villus atrophy and
osteoporosis.
She was suffering from hair loss, poor skin and chronic
fatigue, but had a good attitude. The specialist asked how
strict her gluten-free diet was. After being told she was still eating the odd amount every
month, she was told to cut out gluten completely. A year later her energy was a bit better
and her antibody results were high normal instead of sky-high, but her endoscopy results
were still bad and she still had hair loss and osteoporosis.
The specialist agreed she was indeed on a gluten free diet but then discovered the lady
was a Nun, and she was eating a small piece of host (sacramental bread) daily. The
specialist met the priest and asked for a sample of the host. The specialist measured it
and found that a 30 mg fragment of wafer contains approximately 0.5mg of gliadin (1 mg
of gluten).
The woman refused to give up her daily sacrament until her priest prevailed on her to do
so. Eighteen months later the woman came back radiant with a full head of hair, a healthy
small intestine and no chronic fatigue.
The fragment of the wafer was half a thumb size.

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FACT 5: Autoimmune Disorders occur ten times more commonly in people with celiac disease
(CD) than in the normal population. CD triggers the production of autoimmune antibodies
that attack other organs. CD initiated autoimmune disorders are likely to be misdiagnosed.
(CD is also correlated with many non-Autoimmune Disorders.)
Autoimmune diseases are the third leading cause of
morbidity and mortality in the industrialised world,
surpassed only by cancer and heart disease. Annals
of the rheumatic diseases Sept 2007
Autoimmune disorders are believed to affect
approximately 8 percent of the US population or 24
illio people. That s ore people tha are affe ted
by heart disease (22 million) or cancer of all forms (9
million). This suggests autoimmune disorders may
be the number one cause of death in the U.S.
NIH. Autoimmune Diseases Coordinating
Comm.Autoimmune Diseases Research Plan. 2006
Autoimmune disorders occur 10 times more commonly in CD than in the ge eral populatio .
The autoimmune disorders most frequently associated with CD are type 1 diabetes mellitus and
autoimmune thyroiditis. The presence of celiac disease in type I diabetes, for instance, is
approximately twenty-times higher than in the general population. The autoimmune antibodies
associated with CD include anti-endocrine, anti-gastrointestinal, anti-nuclear, anti-cytoskeleton
and anti-neurological antibodies.
CD is believed to trigger autoimmunity through a variety of mechanisms including HLA and non-
HLA genes, mimicry, altered intestinal permeability, epitope spreading and others. One study
suggested long duration exposure to gluten products is associated with higher rates of
autoimmunity in celiac disease.
The longer celiacs are exposed to gluten the greater the risk they have of developing an
autoimmune disorder.
Our data show for the first time that the prevalence of autoimmune disorders in
Coeliac disease is related to the duration of exposure to gluten
Gastroenterology August 1999

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The age the patient was
Diagnosed with CD
The presence of other
autoimmune condition in
addition to CD
2 5%
2-4 11%
4-12 17%
12-20 27%
>20 34%
Unfortunately most people with celiac disease spend 5-10 years going from doctor to doctor
before a correct diagnosis is made.
Other Disorders
CD is linked with many other diseases including liver and heart diseases, osteoporosis,
myopathies, schizophrenia, small- fibre neuropathy and more: Celiac disease was associated
with an 8-fold increased risk of death from liver cirrhosis. A gluten free diet, however,
normalizes the levels of serum transaminases in 75% to 95% of patients with CD. One study
found osteoporosis patients. In fact, the rate of celiac disease in osteoporosis is high enough that
some recommend all osteoporosis patients undergo CD screening.
CD triggered inflammation appears may be to cause or contribute to myopathy, a muscle
disorder characterized by muscle weakness. A large epidemiological study involving almost
80,000 individuals suggested that every type of cardiovascular disease (heart attack, heart
failure, stroke, etc.)is increased in patients with untreated celiac disease.
CD may increase risk factors for mental disorders such as schizophrenia. One research study
proposes that schizophrenia is rare in cultures with low gluten consumption. Another
population study, however, did not find a link between schizophrenia and CD. Rates of
depression in CD and gastrointestinal disorders do not appear to be increased relative to
healthy controls.
Peripheral Neuropathy
IgG antibodies were present in 34% and biopsy demonstrated villi destruction (celiac disease) in
9% of people with idiopathic peripheral neuropathy including small-fiber neuropathy. (Another
study, however, concluded the two were not linked.)
However, a large Swedish study involving 14,000 people with celiac disease and 70,000 healthy
controls found increased risk of peripheral neuropathy (but not increased risks of neurological
disorders su h as Parki so s, Alzhei er s, ultiple s lerosis, Hu ti gto s disease a d
myasthenia gravis.)The study authors suggested people with peripheral neuropathy be tested

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for CD. Recent studies suggest a form of peripheral neuropathy called small fiber neuropathy is
common in fibromyalgia.
Gluten sensitivity was present in a third of patients with sensory ganglionopathy, a disorder
characterized by damage to the cranial and spinal ganglia, usually by autoimmune processes.
Autopsies of the three of gluten sensitive, SG patients indicated damage to the dorsal ganglia.
Swedish Studies
Sweden has put its large medical databases to good use in many celiac studies.
Adult celiac disease was associated with increased risk of pancreatitis in another Swedish study.
A large Swedish study found celiac disease to be associated with increased risk of a raft of liver
diseases including hepatitis, liver failure, primary biliary cirrhosis, liver cirrhosis and fibrosis and
fatty liver.
Rates of depression increased after celiac disease (but not before it). Immune dysfunction in
both celiac disease and sarcoidosis was believed to play a role in increased rates of sarcoidosis
in people with celiac disease. Immune dysfunction and inflammation was believed behind
increased rates of kidney disease as well. Even fractures got in the act with the Swedes finding
increased risk of hip and other fractures in people with CD. Increased risks were also found in
diabetes (relatively low risk), thyroid disease and adrenal disease (greatly increased).
FACT 6: NCGS may trigger autoimmunity via gut inflammation or via molecular mimicry - with
no gut involvement at all.
…When the finely tuned trafficking of
macromolecules is dysregulated in genetically
susceptible individuals, both intestinal and
extraintestinal autoimmune disorders can occur…
Nature clinical practice. Gastroenterology
&hepatology Sept 2005
Although research has yet to confirm the link
between autoimmunity and NCGS, the largest
study ever completed on gluten sensitivity suggests
mortality rates are higher for people with non-
celia glute disorder NCG“ tha Coelia disease CD . That suggests it s pro a l just a
matter of time before similar correlations regarding autoimmunity are made in the literature.

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Indeed, the study found that people with gut inflammation (which is characteristic of NCGS) are
also highl likel to suffer fro leak gut hi h is stro gl asso iated ith the o set of
autoimmune disorders.
The GI tract regulates the flow of macromolecules between the gut and the rest of the body.
Some researchers believe the introduction of harmful macromolecules into the blood stream
commonly triggers autoimmune processes, both inside or outside of the gut.
It is also important to understand that even if your gut exhibits no villous atrophy (celiac
disease), and no intraepithelial lymphocytosis (inflammation) in the gut, you can still test
positive for gluten sensitivity (positive IgA and IgG blood tests to gluten) and your gluten
sensitivity may be triggering increased autoimmune antibodies to a whole range of different
organs in the body.
Which specific antibodies you develop may depend on your individual genetic make-up or
eak-li k i the hai .
A tige i i i r is o e ethod it s thought CD auses autoimmunity to organs outside the
gut. As the body becomes sensitised to gluten, it can start to attack a range of molecules that
are similar to gluten, like those associated with the thyroid gland.
The common immunogenetic theories ….are sharing common HLA and non-HLA genes, antigenic
mimicry, damage-induced neoantigen exposure, altered intestinal permeability, idiotype
et ork d sregulatio a d epitope spreadi g
Autoimmunity Reviews Sept 2007
The below autoantibodies have been associated with CD; notice that most do involve the gut.

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According to the latest textbook: Advancing Medicine with Food and Nutrients 2nd
Edition,
correlations between the illnesses below and NCGS have been confirmed in the literature:
 IgA Nephropathy
 Epilepsy
 Myalgia/Myositis
 CerebellarAtaxia
 Peripheral Neuropathy
 Brain atrophy
 Irritable bowel syndrome
 Schizophrenia
FACT 7: Where CD/NCGS has affected the gut, taking gluten out of the diet is NOT be enough
for clinical improvement. The fire of inflammation in the gut must be put out and intestinal
permeability MUST be healed to restore absorption. Taking gluten out stops feeding the fire,
but the inflammatory cascade has a life of its own and gut
permeability continues unless there is a specific healing intervention
Less than half of patients with coeliac disease on a gluten-free diet
have complete normalization of intestinal biopsies, intestinal

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permeability defects, and antibody levels (after a mean of 9.7 years on a GFD).Digestive
diseases and sciences April 2010
It is important to understand that children with CD had a 3 fold increase of long-term mortality
– WHETHER THEY WERE ON A GLUTEN-FREE DIET OR NOT according to American Journal of
Gastroenterology April 2007
This suggests taking gluten out of the diet is not enough. Although the villi of CD patients grows
back after 1 year on a gluten-free diet, the evidence suggests that increased intestinal
permeability and poor absorption – both linked with autoimmunity – is still present. So the gut
must be healed and any inflammatory cascade dealt with even after gluten is removed.
There is a strong activation of immuno-inflammation, both in intestinal biopsy samples and in
peripheral blood cells in patients with active CD, with a high chronic release of various cytokines
and other molecules with vasoactive properties such as interferon- and interleukins 2, 4, and 10
The American Journal of Gastroenterology March2003
Gliadin activation of macrophages was found to up-regulate expression of a panel of
inflammatory genes and result in the secretion of inflammatory cytokines.
The Journal of Immunology Feb 2006
The difficulty of adhering to a gluten-free diet (GFD) can make prognosis difficult. Strict
adherence to a GFD does greatly improve nutritional status but one study found it did not
completely normalize od o positio . Metabolizing B-vitamins, in particular, may be
reduced. Hallert et al. found that even celiac patients on long-term gluten-free diets with
normal gut villi, had reduced plasma B-vitamin (homocysteine) levels. Forty-five percent of
celiac disease patients on a gluten free diet for decades had reduced bone mineral density
(osteoporosis).
Increased rates of disease i di ate that neurological problems can manifest themselves even
he o ert ala sorptio is ot prese t i so e patie ts. While su sta tial i pro e e t i
gut mucosa and other factors did occur 2-4 years after beginning a gluten-free diet, lactase
activity was still reduced. O e stud suggested leak gut as still o o a ear after
beginning a gluten-free diet.
Finally, quality of life measures improve after initiating a gluten-free diet but are still somewhat
reduced relative to the general population, so simply removing gluten, while beneficial, is often
not sufficient to return one to full health.
The Cross-sensitization Factor: Taking gluten out of the diet may not be enough because of
the issue of cross-sensitization.

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Even minute traces of gliadin or their cross-
reactive foods are capable of triggering a
state of heightened immunological activity
in gluten sensitive people.
Journal of neurology, neurosurgery, and
psychiatry.Dec 1997
Cross-sensitization refers to a process
where-by a person becomes sensitized to
new substances. For instance, in gluten
sensitivity, the original sensitivity to proteins
called gliadins found in cereals in the
Triticum genus (wheat, rye and barley) can lead to further sensitization to other produce.
Foods known to cross react with purified gliadins (wheat proteins) make up the entire first line
r e, arle , spelt, o s ilk, he protei plus ilk ho olate a d offee . The other foods o
the chart are commonly eaten on a gluten-free diet where sensitivity may also arise. Some
foods such as oats are prepared in facilities where gluten contamination is common. Even small
traces of gliadin can trigger an immune response in very gluten sensitive people.
FACT 8: The current test for CD not only misses out on testing for cross-sensitized foods but
also ignores the fact that people react to a RANGE of gluten proteins, hence false negatives
are prevalent in the standard Celiac test. Also there are at least 24 celiac-associated auto-
antibodies that could be tested for, not just
gut related autoantibodies
The Standard coeliac test is made up of
three elements:
Two antibodies to parts of the BODY – ie
AUTOIMMUNITY in the gut:
1/ To the endomysium – the sheath which
encloses the villi
2/ To transglutaminase – an enzyme inside
the endomysium
Antibodies to an environmental factor – ie ALLERGY to gluten

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3/ Antibodies to the gluten protein gliadin. Recently this has changed to deamidated gluten
which has been found to be more accurate to diagnose CD, but not NCGS.
Problems With The Current Testing Protocols
(1) Antibodies to endomysium and transglutaminase are EXECELLENT markers for TOTAL
VILLUS ATROPHY (i.e. celiac disease) but are highly unreliable diagnostic markers for the
partial villous atrophy or increased epithelial lymphocytes found in non-celiac gluten
sensitivity (NCGS). Only 24% of patients with partial villous atrophy (NCGS) and coeliac
disease were diagnosed correctly using antibody tests in two studies.
The antibody test to the gluten protein ONLY checks for one TYPE of gluten (called the 33-mer peptide.)
If all you do is check the gluten 33-mer (the standard test) ou ll iss glute se siti it 0% of the ti e.
Studies consistently show that most people with CD react to a range of gluten peptides, some
as strongly as the gluten-33 mer that is typically tested for. Note gluten is found in ALL grains,
however a subset of gluten proteins particularly toxic to some humans are found in wheat, rye
and so on. An assay that includes IgA and IgG antibodies for a range of gluten peptides is
therefore desirable;
Our present results indicate that CD patients are capable of responding to a large array of
gluten peptides. We found that 50% of these patients do not respond to the alpha-GLIA
peptide ut to a di erse set of gliadi a d glute i peptides, i ludi g o el epitopes.
Gastroenterology June 2002
Prevalence
If e take i to a ou t that glute se siti it does t
just cause CD, but also partial villous atrophy and gut
inflammation, AND probably triggers many disorders
outside the gut including autoimmune disorders, AND
the fact that people react to a range of gluten
molecules, not just the one in the standard CD, it begs
the question how much of the population is sensitive to
some form of gluten?
I believe it is between 10% and 35% of the population.
Gluten Sensitivity (GS) is a state of heightened immunological responsiveness to ingested
gluten in genetically susceptible people. It represents a spectrum of diverse manifestations, of
which, the gluten sensitive enteropathy known as CD is one of many. Adverse reactions to the
toxic family of gluten proteins found in wheat, barley, rye, and their derivatives may trigger a
heterogeneous set of conditions, including wheat allergy (IgE), NCGS, and CD, that, combined,
affect between 10 – 35% of the population.
Celiac Disease and Non-Celiac Gluten Sensitivity: the Evolving Spectrum

20. www.TheDr.com
FACT 9: The limited research on dietary intervention and CFS is still mainly based on the
classical approach to food allergy which is IgE mediated. Despite clear evidence for non-IgE
mediated food sensitivities, studies on CFS continue to ignore the research
In the Scandinavian Journal of Gastroenterology in Sept 2012i the paper alled Functional
bowel symptoms, fibromyalgia and fatigue: a food-induced triad? resear hers reported:
I a prospe ti e stud , 8 patie ts referred to our outpatie t li i for i estigatio of
perceived food hypersensitivity were enrolled consecutively…
…Neither IgE-mediated food allergy nor organic pathology could explain the patients'
s pto s.
The above paper did not test for CD, or NCGS nor IgG or IgA cross-sensitised foods and reflects
what Manu et al concluded back in 1993 below, which is essentially that CFS patie ts
assertions that self-reported intolerances to food are mental or emotional in origin.
I tolera e to arious foods is reported ofte patie ts seeki g e aluatio for hro i
fatigue…To assess the prevalence and significance of this phenomenon we studied 200
consecutive patients with chronic fatigue who were given a comprehensive medical and
psychiatric evaluation...
These data suggest that intolerance to multiple foods is probably not a cause or the effect of
chronic fatigue, but rather one of the manifestations of the somatization trait expressed in these
patients.
The International journal of eating disorders. March 1993
The food intolerances in the above study were assessed simply by asking patients which foods
they were intolerant to. In classical IgE allergy, foods cause immediate and obvious reactions
which can easily be self-identified, unlike IgG reactions where identification of the offending
food is much more difficult due to the delayed reaction.
ME/CFS patients may have failed to improve in the studies on the effects of dietary restrictions
quoted below because all gluten or cross-sensitised foods were not adequately restricted and
there were no specific intervention to heal the gut and reduce inflammation.
A 2 -week randomized intervention study was conducted with 52 individuals diagnosed with
CFS. Patients were randomized to either a low sugar low yeast (LSLY) or healthy eating (HE)
dietary interventions…
…In this randomized control trial, a LSLY diet appeared to be no more efficacious on levels of
fatigue or QoL o pared to HE.

21. www.TheDr.com
In the 2012 Trabal et al study in the Spanish Journal Nutrición Hospitalaria inthe authors took a
cross sectional pilot study with 28 patients diagnosed with severe chronic fatigue syndrome and
assessed their dietary eating habits with food frequency questionnaires. The reported that 15
patients were restricting gluten and 22 restricted dairy and they found:
Patie ts reported differe t digesti e s pto s, hi h did ot i pro e ith the use of
e lusio diets, a d o luded:
Dietar restri tio s should e ased o a proven food allergy or intolerance. Dietary
counselling should be based o sou d utritio al k o ledge.
Despite these negative studies, Logan and Wong reported on several studies where dietary
restrictions made a large improvement in ME/CFS patients:
Nisenbaum et al presented an abstract at the American Association for Chronic Fatigue
Syndrome conference in Seattle in January 2001, showing that 54 percent of a sample of CFS
patients had attempted unspecified dietary modifications. Of these individuals who modified
their diet, 73 percent reported dietary changes were beneficial in reducing fatigue.
In an Australian study, CFS patients eliminated wheat, milk, benzoates, nitrites, nitrates, and
food colorings and other additives from their diet…Of the CFS patients who complied, the results
were remarkable: 90 percent reported improvement in the severity of symptoms across multiple
body symptoms, with significant reduction in fatigue, recurrent fever, sore throat, muscle pain,
headache, joint pain, and cognitive dysfunction. Furthermore, the elimination protocol resulted
in a marked improvement in IBS-like symptoms among all patients; a significant finding because
CFS patients have a high rate of IBS.
The results of this study support the findings of Borok published in the South African
Medical Journal over a decade ago. Borok cited a strong correlation between CFS
and the presence of food intolerance. He reported alleviation of chronic fatigue among
CFS patients (n=20) after removing certain foods from the diet, with milk, wheat, and corn
among the top offenders.
Alternative Medicine Review 2001
At the moment, no studies have been done testing ME/CFS patients correctly for CD and NCGS,
nor have there been studies testing the effectiveness of introducing a strict gluten-free diet and
with a gut healing anti-inflammatory intervention.

22. www.TheDr.com
FACT 10: Every Person With Chronic Fatigue Syndrome Should Be Screened for Coeliac
Disease and Non Celiac Gluten Sensitivity as Part of the Differential Diagnosis of the
Condition
Many factors suggest CD and NCGS should be part of the differential
diagnosis of ME/CFS.
Neurological symptoms are common. Back in 1999, Luostarinen et
al, in European Neurology, stated that CD should be considered in
all patients presenting with neurological disturbances such as
memory deficits and ataxia of unknown etiology.
Small-fibre neuropathy and muscle pain can be induced by gluten
sensitivity. Symptoms of small-fibre neuropathy such as tingling,
burning pain and tightness, stabbing pain, pins and needles,
itchiness and intermittent numbness in different parts of the body, are commonly experienced
in ME/CFS. Gluten triggered autoimmune ganglioside antibodies can produce all these
symptoms.
Rituximab and other studies suggest autoimmunity is likely to be present in a subgroup of
ME/CFS patients. Chronic disorders such CD and NCGS which cause B Lymphocytes activation
could trigger autoimmune processes in the body. Some ME/CFS patients could have improved
when Rituximab knocked out gluten triggered B lymphocyte activation.
Several studies suggest ME/CFS is an inflammatory disorder. The landmark 2000 Lancet study
that identified non-IgE mediated food intolerances demonstrated that individuals with non-IgE
mediated food intolerance had a significant elevations in inflammatory cytokines (interleukin-4,
interferon gamma, TNF-α) when given a dietary challenge of dairy and wheat.
The authors noted that cytokine elevations could account for the post-challenge symptoms
experienced such as headache, myalgia, joint pain, and gastrointestinal disturbance – all of
which are common in ME/CFS.
We found that food provocation in food intolerant patients was characterised by a general
and systemic immune activation accompanied by an increase in systemic symptoms. Our
findings might be important for the understanding of the mechanisms involved in the
pathogenesis of food intolerance.
The Lancet July 2000

23. www.TheDr.com
Other more direct links to coeliac disease and chronic fatigue syndrome exist. critique of the
diagnostic criteria for ME/CFS asked why ruling out CD was not included. Skoweraet.al. found a
high prevalence of markers of Celiac disease in 100 CFS patients in 2001.
given our prevalence of 2%, and the fact that there is a treatment for CD, we now
suggest that screening for CD should be added to the relatively short list of mandatory
investigations in suspected cases of CFS. “ko era et. al. 2001
As we have discussed sensitivity to gluten is likely to much higher than 2% in the CFS
population, as CD is characterized by total villous atrophy and thus misses out the gluten
se siti e i di iduals ith partial or o illous atroph . We e also sho that a issed
diagnosis of gluten sensitivity is more dangerous than a diagnosis of Celiac disease since
individuals with gluten sensitivity but not celiac disease will probably maintain a state of gut
inflammation that can trigger neurological, autoimmune and other issues.
This probably also explains why another preliminary paper in the International journal of clinical
practice in 2001, found no link between CD and Chronic Fatigue Syndrome.
Why You Pro a ly Are t Getti g this I for atio Fro Your Doctors
Why is celiac disease so little discussed in the ME/CFS Community? The same reason that many
ME/CFS patients are probably not particularly aware of Ehlers Danlos Syndrome or Chiari
malformation or many alternative health treatments.
First of all gastroenterologists tend to read Journals directly related to well
to…gastroe terolog . The do t ha e ti e to read the Jour als i Hepatolog , I u olog ,
Pathology or Nutrition, and therefore they are not connecting the dots and miss out on vital
information that does in fact relate to their practices from other medical specialities.
Second, Doctors in general have limited time and therefore focus on their specialties and much
doctor education comes from drug company representatives showing them the papers which
support their latest drug treatments.
Third nutrition is not given a high priority in medical school. I have spent 10 years collating and
synthesising data on gluten sensitivity. In medical school, doctors are only required to complete
just 25 hours of training in nutrition. And:
Only 28 (27%) of the 105 Medical Schools met the minimum 25 required hours of nutrition
education set by the National Academy of Sciences; 6 years earlier, in 2004, 40 (38%) of 104
schools did so.
Academic Medicine, Vol. 85, No. 9 / September 2010
Finally, some of this information is cutting edge, and cutting-edge information can take decades
to filter do fro the resear h field to the sta dard ph si ia s offi e. In the 1970s it was

24. www.TheDr.com
estimated the time it took for published research to be applied in clinical practice with patients
was about 65 years! With the internet, this has probably more than halved.
I o lusio , it s ot our Do tor s fault – she/he is overworked as it is and is dealing an
alread er o ple disorder. The a t e e pe ted to e o top of e er thi g. Therefore, as
e all k o it s est to get edu ated, take this i for atio to our Do tor if eeded a d do t
wait around for 30 years before your Doctors finally give YOU the information.
I Have Chronic Fatigue Syndrome – What Can I Do To Determine if I
have Celiac Disease or Non-Celiac-Gluten Sensitivity?
How Do I Get Tested?
First, have the blood test done for CD. If that comes back negative, check for NCGS first by
Array #3 antibody testing from Cyrex Labs. If that s not available, a trial period of eliminating
gluten is rational.
If you are having an endoscopy/biopsy done request that an IEL (Intraepithelial lymphocytes)
count be done to assess inflammation in the gut. Most pathologists do t do it ut it s eas a d
inexpensive (about $40). This test will determine if you fall into the inflammatory sub-clinical
group of NCGS patients.
If the Array 3 comes back positive, you can then request Array 4 from Cyrex labs to test for
cross-sensitized foods. The lab automatically saves the original blood sample for 3 months so
another blood sample is not needed.
You may already know you have some form of gluten sensitivity; to confirm this, do the same
test as above. Note: do t orr if ou ha e ot eate glute efore doi g the test a d do ot
go back on gluten for the test because it can have very adverse effects on some patients. Much
of the time, even if you thought you were gluten-free, ou e pro a l still ee exposed,
unknowingly and this testing will confirm that.
In the UK and Europe Regenerus Labs offer the Cyrex Labs testing.
How Do I Follow a Gluten-Free Diet?
An important fact is that mortality rates rise after the first year of going gluten-free possibly
due to gluten withdrawal and because blood sugar problems arise as some people start to skip
meals.
Cardiovascular disease was the most common cause of death in Coeliac disease,
followed by malignancy. The highest HRs were seen in the first year after biopsy, with an HR of
3.78 for death due to malignancy and 1.86 for CV death.
Journal of the American Medical Association.

25. www.TheDr.com
I re o e d a Modified glute -free diet, hi h is esse tiall a glute -free diet designed to
manage blood sugar imbalances and the crashes which often occur in the early withdrawal
phase from gluten. A low sugar diet, meals five time per day and other standard
recommendations to manage blood sugar levels are needed to prevent blood sugar falling to
low or rising too quickly leading to crashes.
Following a gluten-free diet where even that crouton in your salad can cause problems takes
time to master. Did you know gluten is present in cosmetics and personal hygiene products
too? The glute does t ge erall go through our ski u less it has ee through a o-
technology), instead it gets inhaled with similar adverse effects as oral consumption.
For more details of my products and further support on moving to a gluten-free diet see
www.TheDr.com

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